Fitz and Lupe are part of the NCR, so having a low reputation with the Republic will make them hostile.

If the Courier has a negative reputation with the Legion, a group of Legionary assassins may spawn behind the overpass. Fast-traveling to the location or approaching from the south will cause Lupe and Fitz to run out into the road and attack them. Depending on level, the assassins will likely be far more powerful and make short work of them if left to their own devices.

Fitz tells the Courier that most of their customers are NCR citizens traveling from the 188 trading post.

Both Lupe and Fitz can run off and essentially disappear if a Legion assassination party initiates combat near them.